The long term objective of this application is for the candidate to become an independent investigator studying promising new neuroprotective botanical treatments for multiple sclerosis (MS) in human subjects using advanced MRI imaging measures. Axonal loss is thought to be the cause of irreversible progression of disability in MS. None of the available therapies for MS directly protect axons. Epigallocatechin gallate (EGCG) is a potent antioxidant and is the main component contained in polyphenon E, an extract from the leaves of the green tea plant (Camellia sinensis). Animal studies done by our group indicate that EGCG protects axons in the spinal cord from injury in an animal model of MS, experimental autoimmune encephalitis. The overall objective of this application is to determine if polyphenon E is a safe neuroprotective therapy that warrants further study as a treatment to prevent the progression of disability in MS. To achieve this objective, a double-blind, controlled, two-arm parallel group clinical trial will be conducted; 46 subjects with MS will be treated for two years with either polyphenon E 400 mg twice a day or placebo. The first specific objective is to determine if there is evidence of a neuroprotective effect. To accomplish this objective the difference between the two groups on the rate of change in n-acetyl aspartate (NAA) will be determined. NAA was selected as the primary outcome because it is a selective marker for neurons and axons that reflects their number and metabolic activity and thus is optimal to show a neuroprotective effect. NAA levels will be measured using magnetic resonance spectroscopy at baseline, six months, a year and two years. Changes in magnetization transfer ratio and brain atrophy will be secondary outcomes. The second specific objective is to determine the safety of polyphenon E in subjects with MS. The subjects will be monitored for adverse events with laboratory exams and physical exams. The third specific objective is to determine if plasma levels of EGCG predict changes in the imaging markers or the occurrence of adverse events. Conducting this study will allow the candidate to obtain extensive training advanced magnetic resonance techniques and pharmacokinetics. Relevance to public health: MS is the second most common cause of neurological disability among young people. This study is relevant to public health because it is expected to result in a new treatment for MS that can prevent the progression of disability.